Medicaments containing vardenafil hydrochloride trihydrate

• US 8,273,876 B2
• Filed: 07/03/2003
• Issued: 09/25/2012
• Est. Priority Date: 07/16/2002
• Status: Active Grant

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Inventors: Grunenberg, Alfons, Ohm, Andreas, Bellinghausen, Rainer, Vollers, Eimer, Serno, Peter, Henck, Jan-Olav
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Singh, Randeep
• Application Number:
  US10/521,534
• Publication Number:
  US 20060111354A1
• Time in Patent Office: 3,372 Days
• Field of Search: None
• US Class Current: 544/184
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2893 Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention relates to a method for producing medicaments that contain vardenafil hydrochloride, essentially as trihydrate in solid form, and to medicaments that can be obtained according to this method.

Claims

1. A method for producing medicaments in the form of a coated tablet comprising vardenafil hydrochloride trihydrate and one or more excipients, said method comprising the steps of

a) providing a tablet containing vardenafil hydrochloride, irrespective of which polymorphic form or mixture of polymorphic forms of vardenafil hydrochloride is initially present in the tablet, plus one or more excipients including a disintegrant;

b) treating said tablet with a moistened gas for sufficient time to convert at least 90 mol % of the vardenafil hydrochloride into the trihydrate form; and

c) coating said tablet with a coating agent.

2. The method as claimed in claim 1, wherein air is employed as the moistened gas.

3. The method as claimed in claim 2, wherein the moistened gas has a relative humidity of from 35% to 100%.

4. A method for the treatment of erectile dysfunction comprising administering to a subject an effective amount of the coated tablet made by the method of claim 1.

5. A method for the treatment of sexual dysfunctions comprising administering to a subject an effective amount of the coated tablet made by the method of claim 1.

6. The method of claim 3, wherein the moistened gas has a relative humidity of from 50% to 99%.

7. The method of claim 3, wherein said tablet is treated with the moistened gas for from 0.5 hours to 6 months.

8. The method of claim 3, wherein said tablet is treated with the moistened gas at temperatures of 16 to 30°

C.

9. The method of claim 1, wherein said disintegrant is selected from the group consisting of microcrystalline cellulose, crospovidone, and mixtures thereof.

10. The method of claim 1, wherein said coating agent is selected from the group consisting of hypromellose, macrogol, and mixtures thereof.

11. The method of claim 1, wherein said coated tablet as produced contains a disintegrant and a coating agent, wherein the disintegrant is selected from the group consisting of microcrystalline cellulose, crospovidone, and mixtures thereof, and the coating agent is selected from the group consisting of hypromellose, macrogol, and mixtures thereof.

12. A method for producing medicaments in the form of a coated tablet comprising vardenafil hydrochloride trihydrate and one or more excipients, said method comprising the steps of

a) providing a tablet containing vardenafil hydrochloride, irrespective of which polymorphic form or mixture of polymorphic forms of vardenafil hydrochloride is initially present in the tablet, plus one or more excipients including a disintegrant;

b) coating said tablet with a coating agent; and

c) treating said tablet with a moistened gas for sufficient time to convert at least 90 mol % of the vardenafil hydrochloride into the trihydrate form.

13. The method as claimed in claim 12, wherein air is employed as the moistened gas.

14. The method as claimed in claim 13, wherein the moistened gas has a relative humidity of from 35% to 100%.

15. A method for the treatment of erectile dysfunction comprising administering to a subject an effective amount of the coated tablet made by the method of claim 12.

16. A method for the treatment of sexual dysfunctions comprising administering to a subject an effective amount of the coated tablet made by the method of claim 12.

17. The method of claim 12, wherein said disintegrant is selected from the group consisting of microcrystalline cellulose, crospovidone, and mixtures thereof.

18. The method of claim 12, wherein said coating agent is selected from the group consisting of hypromellose, macrogol, and mixtures thereof.

19. The method of claim 12, wherein said coated tablet as produced contains a disintegrant and a coating agent, wherein the disintegrant is selected from the group consisting of microcrystalline cellulose, crospovidone, and mixtures thereof, and the coating agent is selected from the group consisting of hypromellose, macrogol, and mixtures thereof.